Early and longitudinal microglial activation but not amyloid accumulation predict cognitive outcome in PS2APP mice

Focke, Carola; Blume, Tanja; Zott, Benedikt; Shi, Yuan; Deussing, Maximilian; Peters, Finn; Schmidt, Claudio; Kleinberger, Gernot; Lindner, Simon; Gildehaus, Franz-Josef; Beyer, Leonie; von Ungern-Sternberg, Barbara; Bartenstein, Peter; Ozmen, Laurence; Baumann, Karlheinz; Dorostkar, Mario M; Haass, Christian; Adelsberger, Helmuth; Herms, Jochen; Rominger, Axel Oliver; ... (2019). Early and longitudinal microglial activation but not amyloid accumulation predict cognitive outcome in PS2APP mice. Journal of nuclear medicine, 60(4), pp. 548-554. Society of Nuclear Medicine 10.2967/jnumed.118.217703

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Neuroinflammation may have beneficial or detrimental net effects on the cognitive outcome of Alzheimer's disease patients (AD). 18kDa translocator protein (TSPO) imaging by positron-emission-tomography (PET) enables longitudinal monitoring of microglial activation in vivo. We compiled serial PET measures of TSPO and amyloid with terminal cognitive assessment (water maze) in an AD transgenic mouse model (PS2APP) from eight to 13 months of age, followed by immunohistochemical analyses of microglia, amyloid and synaptic density. Better cognitive outcome and higher synaptic density in PS2APP mice was predicted by higher TSPO expression at eight months. The progression of TSPO activation to 13 months also showed a moderate association with spared cognition, but amyloidosis did not correlate with the cognitive outcome, regardless of the timepoint. This first PET investigation with longitudinal TSPO- and amyloid-PET together with terminal cognitive testing in an AD mouse model indicates that continuing microglial response seems to impart preserved cognitive performance.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine

UniBE Contributor:

Rominger, Axel Oliver

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0161-5505

Publisher:

Society of Nuclear Medicine

Language:

English

Submitter:

Sabine Lanz

Date Deposited:

15 Apr 2019 15:46

Last Modified:

22 Oct 2019 22:48

Publisher DOI:

10.2967/jnumed.118.217703

PubMed ID:

30262517

Uncontrolled Keywords:

Amyloid-PET; Animal Imaging; Neurology; PET; TSPO-PET; neuroinflammation; synaptic density; water maze

BORIS DOI:

10.7892/boris.125651

URI:

https://boris.unibe.ch/id/eprint/125651

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